The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals ...and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented.
Dynamical quantum phase transitions are closely related to equilibrium quantum phase transitions for ground states. Here, we report an experimental observation of a dynamical quantum phase transition ...in a spinor condensate with correspondence in an excited state phase diagram, instead of the ground state one. We observe that the quench dynamics exhibits a nonanalytical change with respect to a parameter in the final Hamiltonian in the absence of a corresponding phase transition for the ground state there. We make a connection between this singular point and a phase transition point for the highest energy level in a subspace with zero spin magnetization of a Hamiltonian. We further show the existence of dynamical phase transitions for finite magnetization corresponding to the phase transition of the highest energy level in the subspace with the same magnetization. Our results open a door for using dynamical phase transitions as a tool to probe physics at higher energy eigenlevels of many-body Hamiltonians.
Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified ...associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, α-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
Highlights • Gastrodin improves learning and memory abilities of Tg2576 mice. • Gastrodin attenuates intracellular oxidative stress in hippocampi of Tg2576 mice. • Gastrodin suppresses BACE1 ...expression and PKR/eIF2α pathway in hippocampi of Tg2576 mice. • Gastrodin suppresses BACE1 via inhibiting PKR/eIF2α in SH-SY5Y cells under oxidative stress.
Origami structures are mechanical metamaterials with properties that arise almost exclusively from the geometry of the constituent folds and the constraint of piecewise isometric deformations. Here ...we characterize the geometry and planar and nonplanar effective elastic response of a simple periodically folded Miura-ori structure, which is composed of identical unit cells of mountain and valley folds with four-coordinated ridges, defined completely by two angles and two lengths. We show that the in-plane and out-of-plane Poisson's ratios are equal in magnitude, but opposite in sign, independent of material properties. Furthermore, we show that effective bending stiffness of the unit cell is singular, allowing us to characterize the two-dimensional deformation of a plate in terms of a one-dimensional theory. Finally, we solve the inverse design problem of determining the geometric parameters for the optimal geometric and mechanical response of these extreme structures.
Phytases are a group of enzymes capable of releasing phosphates from phytates, one of the major forms of phosphorus (P) in animal feeds of plant origin. These enzymes have been widely used in animal ...feed to improve phosphorus nutrition and to reduce phosphorus pollution in animal waste. This review covers the basic nomenclature and crystal structures of phytases and emphasizes both the protein engineering strategies used for the development of new, effective phytases with improved properties and the potential biotechnological applications of phytases.
The aims of this retrospective study were to report the feasibility of using 3D-printing technology for patients with a pelvic tumour who underwent reconstruction.
A total of 35 patients underwent ...resection of a pelvic tumour and reconstruction using 3D-printed endoprostheses between September 2013 and December 2015. According to Enneking's classification of bone defects, there were three Type I lesions, 12 Type II+III lesions, five Type I+II lesions, two Type I+II+III lesions, ten type I+II+IV lesions and three type I+II+III+IV lesions. A total of three patients underwent reconstruction using an iliac prosthesis, 12 using a standard hemipelvic prosthesis and 20 using a screw-rod connected hemipelvic prosthesis.
All patients had an en bloc resection. Margins were wide in 15 patients, marginal in 14 and intralesional in six. After a mean follow-up of 20.5 months (6 to 30), 25 patients survived without evidence of disease, five were alive with disease and five had died from metastatic disease. Complications included seven patients with delayed wound healing and two with a dislocation of the hip. None had a deep infection. For the 30 surviving patients, the mean Musculoskeletal Society 93 score was 22.7 (20 to 25) for patients with an iliac prosthesis, 19.8 (15 to 26) for those with a standard prosthesis, and 17.7 (9 to 25) for those with a screw-rod connected prosthesis.
The application of 3D-printing technology can facilitate the precise matching and osseointegration between implants and the host bone. We found that the use of 3D-printed pelvic prostheses for reconstruction of the bony defect after resection of a pelvic tumour was safe, without additional complications, and gave good short-term functional results. Cite this article: Bone Joint J 2017;99-B:267-75.
Malignant cells support tumor proliferation and progression by adopting to metabolic changes. Tumor cells altered metabolism by increasing glucose uptake and fermentation of glucose to lactate, even ...in the aerobic state and the presence of functioning mitochondria. Glucose metabolism in tumor plasticity has attracted great interests by clinicians and scientists in the past decades. This review discusses the previous and emerging researches on the tumor plasticity altered by changing glucose metabolism in different cancer cells, including cancer stem cells (CSCs). In addition, we summarize the rising applications of glucose metabolism in tumor diagnosis and treatment. Our objective is to direct future investigation on this altered metabolic phenotype and its application in patient care.
Both endoscopic obturation and transjugular intrahepatic portosystemic shunts (TIPSs) have proven to be effective in preventing rebleeding from gastric varices. This study compared the efficacy and ...complications of these modalities.
Cirrhotic patients with acute bleeding from gastric varices were considered for inclusion. After initial control, eligible patients were randomly allocated to two groups: TIPS (n = 35) and obturation using cyanoacrylate (n = 37). In the cyanoacrylate group, treatment was repeated regularly until gastric varices were obliterated. Patients of both groups received regular follow-up. The end points were gastric variceal rebleeding or death.
Stent shunt insertion was successful in all TIPS patients, and mean portal pressure gradient decreased from 21.4 +/- 7.5 mm Hg to 7.5 +/- 3.5 mm Hg ( P < 0.001). Variceal obliteration was achieved in 19 patients in the cyanoacrylate group (51 %) compared with seven TIPS patients (20 %) ( P < 0.02). After a median follow up of 33 months, upper gastrointestinal bleeding occurred in 15 TIPS patients (43 %) and 22 cyanoacrylate patients (59 %) ( P = 0.12). Rebleeding from gastric varices was encountered in four TIPS patients (11 %) and 14 cyanoacrylate patients (38 %) ( P = 0.014; odds ratio 3.6, 95 %CI 1.2 - 11.1). Blood transfusion requirements were lower in the TIPS group than in the cyanoacrylate group ( P < 0.01). Survival and frequency of complications were similar in both groups.
TIPS proved more effective than glue injection in preventing rebleeding from gastric varices, with similar survival and frequency of complications.
Reliable assignment of an unknown query sequence to its correct species remains a methodological problem for the growing field of DNA barcoding. While great advances have been achieved recently, ...species identification from barcodes can still be unreliable if the relevant biodiversity has been insufficiently sampled. We here propose a new notion of species membership for DNA barcoding—fuzzy membership, based on fuzzy set theory—and illustrate its successful application to four real data sets (bats, fishes, butterflies and flies) with more than 5000 random simulations. Two of the data sets comprise especially dense species/population‐level samples. In comparison with current DNA barcoding methods, the newly proposed minimum distance (MD) plus fuzzy set approach, and another computationally simple method, ‘best close match’, outperform two computationally sophisticated Bayesian and BootstrapNJ methods. The new method proposed here has great power in reducing false‐positive species identification compared with other methods when conspecifics of the query are absent from the reference database.
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